Assessing the Prognostic Significance of High-Risk Human Papillomavirus DNA and p16INK4a Immunohistochemistry in Anal Cancer: A Systematic Review

Abstract

Background: Anal squamous cell carcinoma (SCC) is increasingly linked to high-risk human papillomavirus (HPV) infection. This systematic review evaluates the prognostic significance of HPV and p16INK4a expression in anal SCC. Methods: A comprehensive literature search identified studies examining the relationship between HPV status, p16 expression, and clinical outcomes in anal SCC patients. Data on study design, sample size, and outcomes related to locoregional control and survival were extracted. Results: Ten studies involving 589 patients were included. High-risk HPV was detected in 80-93% of cases, with p16 positivity significantly associated with improved locoregional control and overall survival. HPV+/p16+ tumors showed superior outcomes compared to HPV−/p16− cases. Both HPV and p16 status were confirmed as independent prognostic markers. Conclusions: HPV and p16INK4a expression are critical prognostic indicators in anal SCC, suggesting their integration into clinical practice for improved treatment stratification. Further prospective studies are needed to validate these findings.